1. Field of the Invention
The present invention generally relates to iontophoretic devices for delivery of drugs or medicines to patients transdermally, i.e., through the skin, and more particularly relates to an iontophoretic drug delivery device having low-cost electrodes and which are easy to manufacture.
2. Background of the Invention
Iontophoretic drug delivery systems, have, in recent years, become an increasingly important means of administering drugs.
Presently there are two types of transdermal drug delivery systems, i.e., xe2x80x9cpassivexe2x80x9d and xe2x80x9cactive.xe2x80x9d Passive systems deliver drug through the skin of the patient unaided, an example of which would involve the application of a topical anesthetic to provide local pain relief. Active systems, on the other hand, deliver drug through the skin of the patient through the application of an electromotive force (iontophoresis) to drive ionizable substances (medicament) into the skin so that they can be absorbed by adjacent tissues and blood vessels. Such systems offer advantages clearly not achievable by other modes of administration, such as hypodermic injection which has the associated problem of pain, risk of infection and trauma to the patient as well as avoiding introduction of the drug through the gastrointestinal tract which has problems of inactivation of the medicament.
Conventional iontophoretic devices, such as those described in U.S. Pat. No. 4,820,263 (Spevak, et al.), U.S. Pat. No. 4,927,408 (Haak, et al.) and U.S. Pat. No. 5,084,008 (Phipps), the disclosures of which are hereby incorporated by reference, provide for delivery of a drug or medicament transdermally through iontophoresis. Basically, conventional iontophoretic devices consist of a power source connected to two electrodes, an anode and a cathode, which are individually in ionic contact with an electrolyte or drug reservoir which is in contact with the skin to be treated by the iontophoretic device. When the current is turned on, electrical energy is used to assist in the transport of ionic molecules into the body through the skin, via ionic conduction.
Delivering drugs via iontophoresis was recognized long ago, however, due to several disadvantages and limitations the use iontophoretic drug delivery devices have not enjoyed widespread acceptance in the medical field. One reason is because a practical commercially feasible iontophoretic transdermal drug delivery device is still not available. Two major impediments with respect to iontophoretic devices are cost of manufacture and reliability. As previously noted, one problem encountered in the clinical use of transdermal drug delivery devices is that presently available devices have not been particularly economical. Generally, other methods of administration of medicaments have been less expensive and easier to use. Considerations such as cost, reliability and convenience have also impeded the general acceptance of transdermal drug delivery devices. Many iontophoretic systems include expensive electrode systems, such as Ag anode and AgCl cathode, electronic controls and sophisticated designs which are difficult to manufacture cost effectively.
One of the key components of an iontophoretic patch contributing to the high cost of the device is the electrode system. The problem of the high cost of the electrode system is particularly acute for electrodes being used for long duration iontophoresis (hours) and high current density ( greater than 50 xcexcA/cm2) applications. Accordingly, there is a need for an electrode system for an iontophoretic drug delivery device which would eliminate the problems and limitations associated with the prior devices discussed above, yet be easy enough to manufacture and also be cost-effective.
It is, therefore, an object of the present invention to provide an electrode system for an iontophoretic device which is inexpensive, easy to manufacture and reliable An electrode system as described herein may include the present inventions as described for the anode electrode, the cathode electrode or both, the anode and the cathode electrodes, of an iontophoretic electrode system.
It is a further object of the present invention to provide an electrode system for an iontophoretic device capable of producing high specific capacity, for example about 1 mA hr/cm2 or greater.
It is yet a further object of the present invention to provide an electrode system for an iontophoretic device having good stability and a prolonged shelf-life.
It is yet a further object of the present invention to provide an electrode system for an iontophoretic device having the benefits of low voltage requirements thereby either eliminating or reducing demand on a system battery.
It is a further object of the present invention to provide a transdermal drug delivery device which utilizes cost-effective materials to form the electrode systems.
It is yet a further object of the present invention to provide a transdermal drug delivery device which is simple, convenient, and economical to manufacture and use.
These and other goals and objectives are satisfied, in accordance with the present invention, wherein one embodiment provides for an iontophoretic electrode assembly comprising an anode patch and a cathode patch.
The anode patch of the iontophoretic electrode assembly which includes an electrode compartment and a skin contact compartment which are in electrical (ionic) communication with one another. The electrode compartment includes an electrolyte and a metal electrode in electrical communication with the electrolyte. The present invention provides one embodiment in which the metal electrode further includes at least two electrochemically active dissimilar metals, such that a first metal provides a coating over a second metal. The coating , bonding and layering discussed herein with respect to the formation of the electrodes can be accomplished using methods known to those having ordinary skill in the art of making iontophoretic electrodes.
The two electrochemically active dissimilar metals form the metal electrode of the anode. An electrochemically active metal, is a metal which is capable of undergoing anodic dissolution (oxidation). Such metals include a bulk base metal, or a non-precious metal or metal composite which are good electron conductors but have limited, if any, chemical inertness. Such bulk metal would be coated with a dissimilar metal, namely, a precious metal or other chemically inert metal. The coating of precious metal (chemically inert metal) prevents the chemical reaction between the base metal and the electrolyte when the anode is in storage or otherwise not use. In this manner, shelf-life of the anode may be extended, while also significantly reducing the cost of manufacturing the electrode, since the electrode is mostly made of non-precious, usually low-cost bulk base metal. In a preferred embodiment, the metal electrode is fabricated substantially from copper, nickel, iron, aluminum, zinc or mixtures thereof which is coated with a layer of silver or other precious or chemically inert metal. An anode formed in accordance with the present invention has been found to exhibit good shelf-life stability as well as good voltage characteristics and stability over a prolonged period of usage in iontophoretic drug delivery devices. Furthermore, in satisfying the objects of the invention, the utilization of a base metal, such as copper, as the bulk material significantly reduces the cost of the anode.
Additionally, the anode of the present invention may be in a solid planar form, by way of example and not limitation, foil, laminates, printed ink on polymeric films and the like; or an open mesh form, by way of example and not limitation, woven, nonwoven screen, expanded foil and the like.
Most preferably the anode is fabricated from an expanded copper foil mesh which is treated with a silver coating. The copper foil mesh provides improved performance and reliability as demonstrated in the examples presented herein. Using silver as only a coating significantly reduces the cost and as the examples cited below demonstrate the electrodes of the present invention perform reliably. The metal electrode is contained in the electrode compartment in communication with the electrolyte.
Another embodiment of the present invention provides for the anode electrode to be formed from essentially one electrochemically active metal which a good electron conductor and chemically inert. By way of example only and not limitation aluminum may be used, since it has both characteristics. Additionally aluminum also reduces manufacturing costs and as the examples cited below demonstrate is reliable as an anodic electrode.
Details concerning some of the structure and function of portions of the iontophoretic device, namely, ion regulating means and compartment separation means, discussed herein below, are described more fully in a co-pending Application, U.S. Ser. No. 08/537,186, filed Sep. 29, 1995 entitled xe2x80x9cImproved Iontophoretic Reservoir Apparatusxe2x80x9d, the disclosure of which is herein incorporated by reference.
Once the iontophoretic electrode assembly is in place on the patient and is activated the metal ions of the metal electrode become positively charged and move toward the skin contacting compartment. In order to keep the metal ions from reaching the skin, the anode may preferably include an ion regulating means which is in ionic communication with the electrolyte and metal electrode. The ion regulating means prevents electrochemically generated metal ions from migrating into the skin contacting compartment of the anode. The anode may also include a compartment separation means, preferably a size exclusion barrier situated between the metal electrode and the skin contacting compartment. The size exclusion barrier substantially prevents contact is of drug ions in the skin contacting compartment from migrating into the electrode compartment and contacting the metal electrode. Both the ion regulating means and size exclusion barrier may be in a variety of known forms and under specific circumstances the ion regulating means may also serve as a compartment separation means.
Another embodiment of the present invention is directed to a novel cathode patch of a patch for use in an iontophoretic electrode assembly. The cathode patch includes an electrode compartment and a skin contacting compartment electrically (ionic) connected to the electrode compartment. The electrode compartment includes an electrolyte containing a soluble, ionizable, reducible metal salt. Examples of such salts include but are not limited to chloride, nitrate and sulfate salts of copper, silver, zinc and iron. The electrode compartment further includes a cathode electrode in electrical communication with the soluble, reducible, ionizable metal salt.
The cathode patch of the present invention has two alternative embodiments with respect to the electrode compartment. In one embodiment, the electrode compartment of the cathode patch, is an electrode comprised of one material, which is both chemically inert as well as a good electron conductor. Such material may for example be precious metals such as platinum, gold, palladium and silver. However, silver is not chemically stable in metal chloride electrolytes (such as zinc chloride or copper chloride) and hence metal chloride salts must be avoided with silver as electrode material. However the use of such a single material may not serve to reduce the cost of manufacturing the device.
Another embodiment of the cathode patch of the present invention is a cathode comprised of a composite of two materials, a good chemically inert material, capable of limited conduction of electrons, in contact with the electrolyte on one side and on the other side in contact with a good electrically (electronic) conductive material, having limited or no chemical inertness. The coating , bonding and layering discussed herein with respect to the formation of the electrodes can be accomplished using methods known to those having ordinary skill in the art of making iontophoretic electrodes.
Additionally, the cathode of the present invention may be in a solid planar form, by way of example and not limitation, foil, laminates, printed ink on polymeric films and the like; or an open mesh form, by way of example and not limitation, woven, nonwoven screen, expanded foil and the like.
In a preferred embodiment, the material having good chemical inertness which by way of example and not limitation may be carbon, palladium, platinum, silver or gold or any other chemically inert material having the ability to conduct electrons. The chemically inert material is coated onto or bonded to any good electrically conductive material, for example, silver, copper, aluminum, zinc, iron, gold, platinum or a variety of known conductive polymers, conductive adhesives or conductive ceramics. Naturally if one trying to keep the cost of manufacturing down then gold and platinum would not be the electrically conductive materials of choice to use.
The cathode electrode compartment contains an electrolyte which has cations present in it for participation in the electrochemical reaction taking place at the cathode. In order to keep these cations from transporting away from the reaction cite and possibly into the skin contacting compartment, an ion regulating means may be used to separate the cathode electrode compartment and the skin contacting compartment, thus, keeping the cations in the cathode electrode compartment.
A complete iontophoretic drug delivery device contains an electrode assembly which comprises an anode patch of an iontophoretic device as described above in conjunction with the cathode patch of an iontophoretic device described above, such that in placing both anode and cathode patches against the skin of a patient completes an electrical circuit with an external power source for driving a medicament into the skin of the patient. As discussed above, iontophoresis involves the application of electric current to drive medicament ions into the skin of a patient. Accordingly, ions bearing a positive charge (placed in the anode skin compartment) may be driven into the skin at the anode of an electrical system and ions bearing a negative charge (placed in the cathode skin compartment) may be driven into the skin at the cathode of the electrical system. Preferred embodiments of the electrodes and a complete iontophoretic drug delivery device, as well as other embodiments, objects, features and advantages of this invention, will be apparent from the following detailed description of illustrative embodiments thereof, which is to be read in conjunction with the accompanying drawings.